Non-invasive screening method for simultaneous evaluation of in vivo growth factor release profiles from multiple ectopic bone tissue engineering implants

• Published in: Journal of controlled release Vol. 130; no. 1; pp. 15 - 21
• Main Authors: Kempen, Diederik H.R., Lu, Lichun, Classic, Kelly L., Hefferan, Theresa E., Creemers, Laura B., Maran, Avudaiappan, Dhert, Wouter J.A., Yaszemski, Michael J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25-08-2008; Elsevier
• Subjects: Absorbable Implants; Animals; Biocompatible Materials - chemistry; Biological and medical sciences; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins - chemistry; Bone Morphogenetic Proteins - pharmacokinetics; Bone Morphogenetic Proteins - pharmacology; Controlled drug delivery; Delayed-Action Preparations; Drug Delivery Systems - methods; Drug Evaluation, Preclinical - instrumentation; Drug Evaluation, Preclinical - methods; Femur - drug effects; Femur - metabolism; Gamma Cameras; General pharmacology; Humans; Iodine Radioisotopes; Male; Medical sciences; Method validation; Non-invasive screening; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Radiolabelled growth factor; Rats; Rats, Inbred Strains; Recombinant Proteins - chemistry; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - pharmacology; Scintillation detector; Tissue Distribution; Transforming Growth Factor beta - chemistry; Transforming Growth Factor beta - pharmacokinetics; Transforming Growth Factor beta - pharmacology; Controlled drug delivery; Non-invasive screening; Scintillation detector; Method validation; Radiolabelled growth factor; Drug; Validation; Evaluation; Pharmaceutical technology; Implant; Tissue engineering; Controlled drug delivery;Non-invasive screening;Scintillation detector;Radiolabelled growth factor;Method validation; Screening; In vivo; Non invasive method; Ectopia; Bone; Release; Growth factor
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2008.05.004

The purpose of this study was to develop and validate a screening method based on scintillation probes for the simultaneous evaluation of in vivo growth factor release profiles of multiple implants in the same animal. First, we characterized the scintillation probes in a series of in vitro experiments to optimize the accuracy of the measurement setup. The scintillation probes were found to have a strong geometric dependence and experience saturation effects at high activities. In vitro simulation of 4 subcutaneous limb implants in a rat showed minimal interference of surrounding implants on local measurements at close to parallel positioning of the probes. These characteristics were taken into consideration for the design of the probe setup and in vivo experiment. The measurement setup was then validated in a rat subcutaneous implantation model using 4 different sustained release carriers loaded with
125I-BMP-2 per animal. The implants were removed after 42 or 84 days of implantation, for comparison of the non-invasive method to ex vivo radioisotope counting. The non-invasive method demonstrated a good correlation with the ex vivo counting method at both time-points of all 4 carriers. Overall, this study showed that scintillation probes could be successfully used for paired measurement of 4 release profiles with minimal interference of the surrounding implants, and may find use as non-invasive screening tools for various drug delivery applications.